The long noncoding RNA MALAT1 suppresses miR-211 to confer protection from ultraviolet-mediated DNA damage in vitiligo epidermis by upregulating sirtuin 1.

BACKGROUND: The absence of melanocytes poses a challenge for long-term tissue homeostasis in vitiligo. Surprisingly, while individuals with Fitzpatrick phototypes I-II (low melanin content) have a higher incidence of melanoma and nonmelanoma skin cancer, people with vitiligo are at a decreased risk for the same. OBJECTIVES: To understand the molecular mechanisms that protect vitiligo skin from ultraviolet (UV)-induced DNA damage by (i) characterizing differentially expressed microRNAs in lesional vs. nonlesional epidermis and (ii) identifying their upstream regulators and downstream gene targets. METHODS: Genome-wide microRNA profiling of nonlesional and lesional epidermis was performed on five individuals with stable nonsegmental vitiligo using next-generation RNA sequencing. The relevance of the upstream regulator and downstream target gene of the most differentially expressed microRNA was studied. RESULTS: Our study found sirtuin1 (SIRT1), an NAD-dependent deacetylase, to be a direct target of miR-211 - the most significantly downregulated microRNA in lesional epidermis. Inhibition of SIRT1 with EX-527 downregulated keratin 10 and involucrin, suggesting that SIRT1 promotes keratinocyte differentiation. Overexpression of miR-211 mimic led to a significant increase in γ-H2AX positivity and cyclobutane pyrimidine dimer (CPD) formation, hallmarks of UVB-mediated DNA damage. These effects could be ameliorated by the addition of resveratrol, a SIRT1 activator. Furthermore, a long noncoding RNA, MALAT1, was identified as a negative upstream regulator of miR-211. Overexpression of MALAT1 resulted in increased expression of SIRT1 and a concomitant removal of UVB-induced CPDs in primary keratinocytes. CONCLUSIONS: These findings establish a novel MALAT1-miR-211-SIRT1 signalling axis that potentially confers protection to the 'amelanotic' keratinocytes in vitiligo.

Usefulness of postexercise ankle-brachial index to predict all-cause mortality.

Peripheral arterial disease predicts future cardiovascular events and all-cause mortality. Conventional methods of assessment might underestimate its true prevalence. We sought to determine whether a postexercise ankle-brachial index (ABI), not only improved peripheral arterial disease detection, but also independently predicted death. This was an observational study of consecutive patients referred for ABI measurement before and after the fixed-grade treadmill or symptom-limited exercise component to a noninvasive vascular laboratory from January 1990 to December 2000. The subjects were classified into 2 groups. Group 1 included patients with an ABI of ≥0.85 before and after exercise, and group 2 included patients with a normal ABI at rest but <0.85 after exercise. A total of 6,292 patients underwent ABI measurements with exercise during the study period. Propensity score matching of the groups was performed to minimize observational bias. Overall mortality, as determined using the United States Social Security death index, was the end point. The 10-year mortality rate of groups 1 and 2 was 32.7% and 41.2%, respectively. An abnormal postexercise ABI result independently predicted mortality (hazard ratio 1.3, 95% confidence interval 1.07 to 1.58, p = 0.008). Additional independent predictors of mortality were age, male gender, diabetes, and hypertension. After the exclusion of patients with a history of cardiovascular events, the predictive value of an abnormal postexercise ABI remained statistically significant (hazard ratio 1.67, 95% confidence interval 1.29 to 2.17, p <0.0001). In conclusion, our results have shown that the postexercise ABI is a powerful independent predictor of all-cause mortality and provides additional risk stratification beyond the ABI at rest.

The "midface-lift" as a misnomer for correctly identifying procedures designed to lift and rejuvenate the cheeks and malar regions of the face.

OBJECTIVE: To demonstrate that a classic temporal cheek rhytidectomy results in substantial and acceptable rejuvenation of the so-called midface and that additional surgery is not necessary to improve a sagging cheek, the melolabial fold, and the position of the corner of the mouth and the lateral corner of the eye. DESIGN: A retrospective observational study of 53 patients seen at the McCollough Plastic Surgery Clinic between 2005 and 2007. Each patient underwent temporal and cheek face-lifting surgery for various indications. All procedures were performed by the same surgeon, and the surgical technique was identical in all cases. Patient photographs were evaluated by 3 unbiased plastic surgeons who were asked to compare preoperative and postoperative elevation of the cheek mound, melolabial fold, oral commissure, and lateral canthus. Each anatomic area was appraised for improvement by each reviewer using a 4-point scale. RESULTS: The average patient age was 57 years, and the average patient follow-up was 11 months. Patients achieved excellent or significant improvement in a sagging cheek, melolabial fold, oral commissure, and lateral canthus in 79% (n = 42), 70% (n = 37), 72% (n = 38), and 65% (n = 34) of cases, respectively. CONCLUSIONS: It has been written often that standard face-lifting techniques fail to address many of the aging changes seen in the cheeks. Many authors argue that a separate, unique procedure is required to effectively rejuvenate the cheek, nasolabial fold, and corner of the mouth. Our experience is contrary to this notion. The middle third facial rejuvenation can be achieved by our standard temporal cheek face-lift, and the term midface-lift may be a misnomer.

Neuroendocrine carcinoma of the jugular foramen.

We describe what might have been the first reported case of a neuroendocrine carcinoma of the jugular foramen. A 50-year-old woman presented with progressive left-sided sensorineural hearing loss, vertigo, pulsatile tinnitus, headaches, and ataxia. Magnetic resonance imaging revealed a 4-cm left-sided jugular foramen tumor. The patient underwent near-total resection of the tumor. Despite lower cranial nerve preservation, postoperative paralysis of cranial nerves IX and X occurred, and vocal fold medialization was performed 5 days later. The final pathologic diagnosis was neuroendocrine carcinoma. The patient was treated with concurrent chemotherapy and intensity-modulated radiation therapy. This article will discuss the pathologic features and the management of jugular foramen tumors, along with the differential diagnosis of these rare tumors.

Surgical management of facial neuromas: lessons learned.

OBJECTIVE: Primary tumors of the facial nerve are rare, representing 1% of all intrapetrous lesions. We analyzed the management and surgical outcomes of 16 patients with multisegment facial neuromas treated at our institution during a 16-year period. STUDY DESIGN: A retrospective chart review. SETTING: Tertiary referral center. PATIENTS: All patients included in the study had surgical management of their facial neuroma. There were 9 women and 7 men. The mean age was 46 years, with a mean follow-up period of 3 years. INTERVENTION: Surgical excision (n = 15) or decompression (n = 1) of facial neuroma. MAIN OUTCOME MEASURES: Tumor location, presenting symptoms, hearing outcomes, and facial function. RESULTS: Thirteen (81%) patients had facial paresis as their presenting symptom. Unilateral hearing loss was present in 9 (56%) patients. Most tumors (n = 15) involved multiple segments of the facial nerve and ranged in size from 1.5 to 7 cm. Fifteen (94%) patients had the tumor completely excised, and 1 (6%) patient underwent needle decompression of the cystic component of the tumor. The geniculate ganglion was the most commonly involved (11 patients, 69%) segment of the nerve, followed by the labyrinthine and tympanic segments. Despite multiple types of reconstructive options used, the best recovery of facial function was a House-Brackmann Grade III in 12 patients. CONCLUSION: Treatment of facial neuromas depends on the extent of tumor, degree of facial paresis, and hearing function. We advocate complete resection of tumor when facial palsy exists. Patients with normal facial function and hearing may be advised on a more conservative treatment option such as radiologic observation, drainage of any cystic component of the tumor for histologic diagnosis, and/or bony decompression of the tumor.

Surgical outcomes following the endoscopic modified Lothrop procedure.

OBJECTIVE: We performed a systematic review of 97 patients in whom an entirely endoscopic modified Lothrop procedure (EMLP) was performed. We studied the safety, efficacy, need for revision surgery, and rate of complication following an EMLP. STUDY DESIGN: The study design was a retrospective chart analysis. METHODS: We performed a retrospective chart review and patient survey of 97 patients who underwent an EMLP at our institution from January 1999 to March 2006. Main outcomes measured were the need for revision surgery including an osteoplastic flap (OPF), improvement in patients' symptoms, and rate of cerebrospinal fluid (CSF) leak. RESULTS: The most common indication for the procedure was chronic frontal sinusitis and/or formation of mucocele. The frontal recess and floor of the frontal sinus were the most common areas of persistent disease. CSF leak rate was 1% (1/97) and was managed successfully at the time of surgery without any long-term sequelae. Twenty-two (23%) patients required revision surgery. Three (3%) patients required revision with an OPF. Some degree of symptomatic clinical improvement was reported by 98% (95/97) of patients. CONCLUSION: EMLP is a safe and effective surgical alternative to OPF for patients with recalcitrant frontal sinus disease. Major complications are rare. A large percentage of patients may require revision surgery.

Activity of nasal amphotericin B irrigation against fungal organisms in vitro.

BACKGROUND: The role of fungi in chronic rhinosinusitis has been described in recent reports. Controversy exists on the use of topical amphotericin B therapy as a treatment modality for this condition. The effect of various concentrations of amphotericin B nasal irrigation on actively growing fungi was studied in vitro. METHODS: Ten species of fungi commonly found in the nasal cavity were grown on growth media plates. Each fungi was exposed to 20 mL of amphotericin B nasal irrigation at concentrations of either 100, 200, or 300 microg/mL or sterile water two times daily for 6 weeks. Each plate was subcultured on a weekly basis to examine for any viable fungi. RESULTS: Fungi growth was not arrested in the 100-microg/mL amphotericin B and sterile water groups at the end of 6 weeks. Use of the 300-and 200-microg/mL amphotericin B solutions showed failure of the subcultured fungi to grow at 5 and 6 weeks, respectively. CONCLUSION: Nasal amphotericin B irrigation is ineffective in killing fungi in vitro at a concentration of 100 microg/mL over a 6-week period. Concentrations of 200 and 300 lig/mL successfully prevented fungi growth at the conclusion of the study. The current concentration of commercially available topical amphotericin B (100 microg/mL) seems ineffective in eradicating fungi in vitro.

The influence of peripheral arterial disease on outcomes: a pooled analysis of mortality in eight large randomized percutaneous coronary intervention trials.

OBJECTIVES: We aimed to evaluate clinical outcomes among peripheral arterial disease (PAD) patients following percutaneous coronary intervention (PCI). BACKGROUND: A significant proportion of patients with coronary artery disease undergoing PCI have concomitant PAD, which may be associated with worse outcomes. METHODS: We performed a pooled analysis of 8 randomized PCI trials. We included multicenter PCI trials that compared antiplatelet therapies (EPIC, EPILOG, EPISTENT, RAPPORT, CAPTURE, IMPACT-II, TARGET, and CREDO) and had baseline PAD status recorded. Multivariable analyses were performed with stepwise logistic regression for 7- and 30-day outcomes and Cox regression for 6-month and 1-year events. RESULTS: In our pooled analysis of 19,867 patients undergoing PCI, 1,602 (8.1%) were previously diagnosed with PAD. Patients with PAD had higher incidences of 7-day death (1.0% vs. 0.4%; p < 0.001) or myocardial infarction (MI) (6.8% vs. 5.6%; p = 0.047), 30-day death (1.7% vs. 0.7%; p < 0.001) or MI (7.4% vs. 6.1%; p = 0.05), 6-month death (4.2% vs. 1.5%; p < 0.001) or MI (9.1%, vs. 7.7%; p = 0.048), and 1-year death (5.0% vs. 2.1%; p < 0.001). There was a trend toward higher major bleeding risk with PAD (4.8% vs. 3.9%; p = 0.06). With multivariable analyses, PAD remains a significant predictor of mortality at 30 days (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.03 to 2.70; p = 0.039), 6 months (HR 1.76, 95% CI 1.31 to 2.37; p < 0.001), and 1 year (HR 1.46, 95% CI 1.08 to 1.96; p = 0.013). CONCLUSIONS: The presence of PAD is associated with higher rates of post-PCI death and MI, and is an independent predictor of short- and long-term mortality.

Surgical treatment of pediatric cholesteatomas.

OBJECTIVE: : Management of pediatric cholesteatomas remains controversial. We reviewed our 16-year experience in the surgical treatment of cholesteatomas in children and describe a treatment paradigm. STUDY DESIGN: : The authors conducted a retrospective review. METHODS: : A total of 106 mastoidectomies (86 for an acquired cholesteatoma and 20 for a congenital cholesteatoma) were performed in children 16 years old and younger from 1988 to 2003. Follow up ranged from 2 years to 12 years with a mean follow-up period of 6 years. Hearing outcomes, cholesteatoma recidivism, and dry mastoid cavity were the main outcomes measured. RESULTS: : Seven (7%) patients had revision surgery for cholesteatoma recidivism. Rates of cholesteatoma recurrence for canal all up (CWU) and canal wall down (CWD) mastoidectomy groups were similar (8% vs. 6%). The percentage of patient with good serviceable hearing (pure-tone average

Perioperative complications with the bone-anchored hearing aid.

OBJECTIVE: To discuss perioperative complications associated with the bone-anchored hearing aid (BAHA) and their management. STUDY DESIGN AND SETTING: A retrospective review of 58 patients who underwent implantation of BAHA for unilateral conductive, mixed, or sensorineural hearing losses was performed at a tertiary referral center. RESULTS: Between September 2003 and June 2005, 58 patients underwent implantation of a BAHA. There were 30 female and 28 male patients, with a mean age of 48 years (range 8-80 years). Complications occurred in 19% (11/58) of patients. Most adverse events were seen early in the series. The most common complication, partial or complete loss of the skin graft, occurred in 10% (6/58) of patients. These were managed successfully with local wound care. Five percent (3/58) of patients had skin growth over the abutment. Two of these cases were managed with office debridement, whereas 1 patient required revision under general anesthesia. There was implant extrusion in 3% (2/58) of patients, and both of these patients later underwent successful reimplantation. All patients had their implant activated 3 months after surgery. There were no perioperative or postoperative deaths. CONCLUSION: Complications related to BAHA implantation are relatively minor and usually involve partial or complete loss of the skin graft. Most complications were successfully managed in the office.

Isolated internal jugular vein thrombosis: risk factors and natural history.

Deep venous thrombosis (DVT) involving the upper extremities, chest, and neck has become appreciated as a significant cause of morbidity, especially in individuals with central venous access devices (CVAD). Like DVT involving the leg and pelvic veins, axillo-subclavian vein thrombosis can result in pulmonary embolism, post-thrombotic syndrome, and venous limb gangrene. Data relating to the natural history of internal jugular vein thrombosis (IJVT) is lacking. Risk factors, treatment patterns, and clinically relevant outcomes were retrospectively assessed in 74 consecutive patients with isolated IJVT. All patients (median age 66 years; range 36-80) had CVAD-associated IJVT, 22 (29.7%) had a history of cancer, and 14 (18.9%) had a history of prior DVT. Thirty-two (43.2%) were treated with systemic anticoagulation, 2 (2.7%) received a superior vena cava filter, and 40 (54.1%) received no specific therapy. Of the patients who underwent serial imaging, 7/40 (17.5%) had thrombus propagation. Two (2.7%) patients were diagnosed with pulmonary embolism, 8 (10.8%) were diagnosed with malignancy during a median follow-up of 20 months (range 18-24), and 3/53 (5.7%) suffered a recurrent DVT. Outcomes similar to those seen in leg DVT were observed. The most effective treatment strategy remains to be determined, but anticoagulant treatment was associated with a trend towards reduced all-cause mortality.